New Drug Reduces Risk of Deadly Side Effects of Bone Marrow Transplant

First Posted: Dec 10, 2012 05:00 AM EST

Bone marrow transplants carry a significant risk of serious complications and developing infections that can multiply over a period of time. Researchers at the University of Michigan Comprehensive Cancer Center have come up with a new class of drugs that reduce the risk of patients contracting these serious side effects.

This study is the first to test this treatment in people. The researchers combined the drug vorinostat with standard medications given after transplant. The scientists noticed that only 21 percent of the patients developed graft-versus-host disease compared to 42 percent of patients who typically develop this condition with standard medications alone.

Graft-versus-host disease (GVHD) is a complication that can occur after stem cell or bone marrow transplantation in which the newly transplanted donor cells attack the recipient's body.

"Graft-versus-host disease is the most serious complication from transplant that limits our ability to offer it more broadly. Current prevention strategies have remained mostly unchanged over the past 20 years. This study has us cautiously excited that there may be a potential new way to prevent this condition," says lead study author Sung Choi, M.D., assistant professor of pediatrics at the U-M Medical School.

The drug Vorinostat has the approval of the U.S Food and Drug Administration to treat certain types of cancer.

The U-M researchers, led by senior study author Pavan Reddy, M.D., found in laboratory studies that the drug had anti-inflammatory effects as well -- which they hypothesized could be useful in preventing graft-versus-host disease, a condition in which the new donor cells begin attacking other cells in the patient's body.

Choi will present data on the first 47 patients enrolled in the study at the University of Michigan Comprehensive Cancer Center and Washington University. These patients were older adults who were undergoing a reduced-intensity bone marrow transplant with cells donated from a relative. 

The researchers made sure that these patients received standard medication used after a transplant to prevent the disease. They also received vorinostat, orally  as pills.

Vorinostat was considered safe and tolerable by researchers, which could be given to vulnerable population, with manageable side effects.

The rate of patient death and cancer deterioration among the study participants was similar to historical averages.

Reddy, an associate professor of internal medicine at the U-M Medical School, has been studying this approach in the lab for eight years.

"This is an entirely new approach to preventing graft-vs.-host disease," Choi says. Specifically, vorinostat targets histone deacetylases, which are different from the usual molecules targeted by traditional treatments.

"Vorinostat has a dual effect as an anti-cancer and an anti-inflammatory agent. That's what's potentially great about using it to prevent graft-vs.-host, because it may also help prevent the leukemia from returning," Choi says.

The researchers hope next to test vorinostat in patients receiving a transplant from an unrelated donor, which carries an even greater risk of graft-vs.-host disease. 

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